The caspase family of cysteine proteases is mainly known for its pivotal role in the induction of apoptosis in animal cells (Shi et al., 2002). Some of the caspases, characterized by a ‘prodomain’ region located upstream of the proteolytic moiety, serve an initiating role in apoptosis. They become activated upon binding of their prodomains to death-inducing receptors or to adapter proteins associated with such receptors, and once activated they cleave other members of the caspase family, thereby activating them. Caspase-8 (previously known as MACH/FLICE/Mch4) is an initiator caspase activated within signaling complexes of receptors of the TNF/NGF family, to which it is recruited by the binding of its prodomain to an adapter protein called Fas-associated death domain (FADD; also called MORT1) (Boldin eta al., 1996, Muzio et al., 1996, and Wallach et al., 1999). Activation of caspase-8 constitutes a crucial initiating event in the apoptotic death mechanism induced by these receptors (the extrinsic cell-death pathway)(Varfolomeev et al., 1998). Both caspase-8 and FADD also contribute, by mechanisms as yet unknown, to various non-apoptotic cellular processes (e.g., see Varfolomeev et al., 1998, Zhang et al., 1998, Walsh et al., 1998, Newton et al., 1998, Alam et al., 1999, Kennedy et al., 1999, Chun et al., 2002, Sakamaki et al., 2002, Salmena et al., 2003, Kang et al., 2004, Su et al., 2005 and Beisner et al., 2005).
Although the in-vivo functioning of caspase-8 has been explored using a number of transgenic mouse models (Varfolomeev et al., 1998, Salmena et al., 2003, Kang et al., 2004, and Beisner et al., 2005), still very little is known about the enzyme's physiological or pathophysiological significance.